1. Field of the Invention
The present invention relates to a method or system of performing experiments and testing therapeutic drugs and experimental procedures on a test animal. In particular, the present invention relates to a system for delivering optical, fluid, and electrical neuronal data to and from a test animal and/or applying one or more procedures to the animal at the same time while compensating for animal movement to prevent, over long times, twisting of the cable connections for fluid exchange and sampling, optical or electrical connections. The system is designed for chronic application and implantation within an animal model (including human) test subject. The system also defines a process and system for creating therapies.
2. Description of Related Art
Multichannel microwire arrays, carbon fibers, microfabricated silicon or ceramic electrode arrays for acquiring neural signals and chemical signals from large numbers of single neurons and from multiple brain or body regions, and for stimulation of brain regions, are known in the art. Arrays usually comprise one or more microwires, multisite probes with specialized chemical sensor sites, or carbon electrodes. One or more connectors, flexible cable connectors with leads, or printed circuit boards are in electrical connection with the electrodes. These connectors are useful for studying higher order functions of the brain and actions of drugs in relation to behavior during stimuli which cannot be determined with single or small numbers of neuronal connections. The brain and body consists of a complex biological system that requires concurrent observation and causal probing at many interconnected sites to reveal function and to develop therapeutic strategies.
While this type of interface is capable of measuring very specific activity of the brain during stimulation or behavioral constraints with a great deal of information being acquired or delivered, the ability to do so with a moving animal subject, such as a mouse or rat has been limited. Originally, the most common method of dealing with an awake animal during measurements was to restrain the subject to prevent them from disturbing contacts of probes with neurons, twisting the connections, and thus, damaging the connections, the animal, or both. This makes long term studies very difficult to conduct and studies where the animal must move to create the stimulus is impossible. This is true for all animal connections including optical, fluid, and electrical connections.
The problem of allowing the animal to move freely while maintaining multiple electrical including video, fluid, or optical connections is exacerbated by the need for a rotating swivel for each type of connection. Frequently, in the past, the problems with the addition of multiple connections to animals during testing was dealt with by use of slip ring bushings which allowed the connecting lines to the high density array each to twist, thus, preventing twisted lines. However, for multiple animals, and in general, the slip rings are expensive to use and to coordinate, may introduce electrical noise, and therefore are a problem of their own.
A similar problem applies to connections needed to control electrical stimulation in multiple areas such as the brain. Also difficult for these reasons is the use of multiple sensors that require a combination of electrical stimulation and recording. Sensors of many types have this common difficulty. These may include combinations of functions for electrical recording, electrical stimulation, chemical sensing, pressure detectors, movement and mechanical deformation sensors, optical stimulation, optical sensing, video capture, sound sensing in the auditory range, ultrasound for imaging, stimulation, and fluid flow measurement. It is clear that the difficulties to be addressed are common to multiple sensor/stimulation systems that need to operate in parallel and that require connections to external instrumentation. Typically, the larger the numbers of connections and type, the more difficulties arise.
Chronic dosing of an animal or sampling of body fluids by attachment of multiple fluid drug sources with a control to regulate the timing and amount of a delivered drug or obtaining a fluid sample is an even greater problem. A rotatable fluid swivel connector is not a very effective means of delivering multiple types of fluid drug doses. They are cumbersome and it is difficult to prevent leaks with multiple fluid connections. Accordingly, the combination of delivering drugs and simultaneously performing multichannel array neuronal readings has been almost impossible to accurately and consistently accomplish over the periods of time necessary to perform drug testing on animals with parallel behavioral assessment. Even further, research with this type of measurement is limited at best and data is not useful enough to be consistently accurate (see e.g. www.Instech.com). Use of lasers to apply light stimulation to multiple sites, and light sensors, scanners or imagers are also burdened with this problem.
Of great use would be a system that allows for administration of therapeutic test drugs and other experimental manipulations while monitoring or stimulating neuronal activity and behavior through multiple modes involving fluids optically or electrically connecting to a moving animal that can easily be accomplished during tests over long periods of time, and especially for simultaneous use with multiple animals to achieve high throughput testing for development of therapies.